Aortic Baroreceptor Deafferentation Research Articles

Effect of aortic baroreceptor deafferentation on plasma vasopressin and oxytocin in the conscious rat

Experiments were done in conscious, unrestrained rats to investigate the effects of selective aortic baroreceptor deafferentation (ABD) on circulating levels of the neurohypophysial hormones arginine vasopressin (AVP) and oxytocin (OXY). Plasma concentration of AVP and OXY were measured by radioimmunoassay before and 1–13 days after cutting the aortic depressor nerves, bilaterally. Arterial pressure was significantly elevated by approximately 12–39 mmHg above control levels after ABD. On day one after ABD, plasma AVP increased from control levels of 3.21 ± 1.56 pg/ml to 8.29 ± 4.66 pg/ml (258%) and plasma OXY increased from 2.53 ± 4.24 pg/ml to 8.16 ± 1.49 pg/ml (323%). However, by the third day after ABD, plasma AVP and OXY levels had returned to pre-ABD control levels. On days 8 and 13 after ABD, AVP levels were elevated again by approximately 2- and 9-fold, respectively, whereas the OXY levels remained at control levels. These data suggest that in the awake rat, the release of AVP and OXY is modulated differentially after ABD and that the increased circulating levels of AVP may be one of the mechanisms that contributes to the elevated arterial pressure in neurogenic hypertension.

Effect of renal denervation on plasma renin activity after aortic baroreceptor deafferentation

Renal nerves are thought to play an important role in cardiovascular regulation under both normotensive and hypertensive conditions. In the present study the effect of renal denervation on the changes in plasma renin activity (PRA) after aortic baroreceptor deafferentation (tADN) were investigated in the rat. Bilateral renal denervation did not alter arterial pressure (AP, 100 +/- 4 mmHg; 1 mmHg = 133.32 Pa), heart rate (HR, 363 +/- 12 bpm), or PRA (2.9 +/- 0.6 ng.mL-1.h-1) compared with the respective sham renal denervation values of 106 +/- 3 mmHg (AP), 385 +/- 13 bpm (HR), and 3.3 +/- 0.7 ng.mL-1.h-1 (PRA). On the other hand, bilateral tADN resulted in significant increases in AP, HR, and PRA. One and 3 days after tADN, AP was 130 +/- 4 and 127 +/- 6 mmHg, HR was 461 +/- 15 and 463 +/- 20 bpm, and PRA was 9.1 +/- 3.0 and 11.9 +/- 4.5 ng.mL-1.h-1, respectively. Renal denervation before tADN prevented the increases in AP and PRA, but it did not affect the increase in HR. These data indicate that renal denervation does not alter basal PRA in normotensive animals but prevents the increased renin release observed in neurogenic hypertension. These data suggest that the increased PRA may be one of several factors that contributes to the elevated AP after tADN.

Forebrain mechanisms in neurogenic hypertension.

In recent years a considerable amount of experimental evidence has suggested that forebrain structures are involved in the pathogenesis of high arterial pressure (AP). However, little is known about the location and function of these supramedullary structures in the hypertensive process. This report reviews a series of studies done to identify the location and to determine the contribution of some forebrain structures to both the development and maintenance of the elevated AP following selective aortic baroreceptor deafferentation (ABD). In the first series of studies, it was demonstrated that the elevated AP resulting from ABD was associated with increased metabolic activity in several forebrain structures: the paraventricular nucleus of the hypothalamus (PVH), supraoptic nucleus, nucleus circularis, median preoptic nucleus, subfornical organ (SFO), and central nucleus of the amygdala. In the second series, bilateral electrolytic lesions of the PVH were shown to prevent the development of and (or) reverse the elevated AP after ABD. Similarly, bilateral microinjections of the neurotoxin kainic acid into the PVH were shown to reverse the increased AP after ABD. In the final series, electrolytic lesions of the SFO were shown to attenuate the rise in AP after ABD and (or) to reduce the elevated AP to a level that remained above control values. Taken together, these data suggest that the PVH and SFO are components of a neuronal circuit involved in the hypertensive process following ABD, and that the SFO likely exerts its effect through the PVH.

Sinoaortic denervation in the nonhuman primate.

There is considerable controversy as to whether removal of baroreceptor input by sinoaortic deafferentation leads to a sustained hypertension in quadripeds. Because of the importance of the baroreflex during postural changes, the effects of baroreceptor denervation may be even more profound in the primate. In this study, six adult male baboons (Papio anubis) were maintained on a tether system to examine the acute and sustained effects of aortic and combined carotid sinus and aortic baroreceptor deafferentation. Mean arterial pressure (MAP) averaged over 24 h increased from 86 +/- 4.0 to 105 +/- 5.5 mmHg after aortic denervation. One week after sinoaortic deafferentation, arterial pressure rose to 129 +/- 12.9 mmHg and then receded to 97 +/- 4.4 mmHg at 4 wk postdenervation. The lability of arterial pressure (measured as the mean of the standard deviations over 24 h) did not change with aortic denervation but increased at 1 and 4 wk after complete baroreceptor denervation. These studies indicate that baroreceptor deafferentation in the primate results in an acute increase in arterial pressure, the lability of arterial pressure, and heart rate. However, by 4 wk postdenervation, the level and lability of arterial pressure are decreased but remain significantly elevated.

Aortic baroreceptor deafferentation diminishes saline-induced drinking in rats

The effect of bilateral surgical deafferentation of the baroreceptors in the aortic arch and carotid sinus on experimentally induced water intake was investigated in rats. Drinking was induced by subcutaneous administration of one of the following agents: hypertonic saline, polyethylene glycol, isoproterenol and angiotensin II, or by 18 h of water deprivation. Hypertonic saline-induced drinking was significantly attenuated after bilateral denervation of either the aortic arch plus the carotid sinus or the aortic arch alone. However, this diminished response disappeared when hypertonic saline was given in subsequent tests. The initial drinking deficit following hypertonic saline was independent of the time elapsed since the animals had undergone surgery. All other thirst challenges tested resulted in water intake that was not statistically different from sham-operated control groups. It is concluded that aortic baroreceptor deafferentation initially results in a diminished drinking response following hypertonic saline, possibly due to interruption of afferent information originating in osmosensitive areas in the aortic arch. A role of arterial baroreceptors in the regulation of non-osmotically induced water intake is not supported by the present data.

Aortic baroreceptor deafferentation in the baboon.

Previous animal studies have indicated that removal of the aortic baroreceptors causes a moderate increase in arterial pressure that is not fully buffered by receptors in the carotid sinus. However, the role of these separate baroreceptors in the conscious nonhuman primate has not been examined. To address this question, adult male baboons were chronically maintained on a tether system that permitted them to move freely about their cage. With this system, arterial pressure and heart rate could be monitored continuously over 24-h periods with periodic drug administration to test cardiovascular function. Control values of arterial pressure and heart rate were 85.6 +/- 4.0 mmHg and 77.5 +/- 2.9 beats/min, respectively. Following removal of the aortic baroreceptors, arterial pressure rose to 104.6 +/- 5.5 mmHg and heart rate increased to 117.9 +/- 3.1 beats/min. The variability of these parameters did not change following denervation. There was, however, a suppression of the arterial pressure-heart period relationship and an augmentation in the depressor response to ganglionic blockade with hexamethonium. These data indicate that removal of the aortic baroreceptors causes a reduction in the sensitivity of the heart rate baroreflex and subsequent increase in arterial pressure that is a result of an increased sympathetic nervous system function.

Effect of paraventricular nucleus lesions on arterial pressure and heart rate after aortic baroreceptor denervation in the rat

Two series of experiments were done in male Wistar rats to investigate the effects of lesions of the paraventricular nucleus of the hypothalamus (PVH) on the maintenance and development of the elevated arterial pressure resulting from denervation of aortic baroreceptors. In the first series, after control recordings of arterial pressure (AP) and heart rate (HR), rats were subjected to either bilateral aortic depressor nerve (ADN) transection or sham-ADN. These animals were later subjected to either bilateral lesions of the PVH or sham-PVH lesions. AP ( 146 ± 2mm Hg) and HR ( 515 ± 5bpm) were significantly elevated in only the ADN-transected groups. Bilateral lesions of the PVH significantly reduced AP ( 119 ± 3mm Hg) and HR ( 440 ± 8bpm) in the ADN transected animals compared to ADN-transected sham-PVH-lesioned animals, to levels which were not significantly different from pre-ADN-transected levels ( AP113 ± 2mm Hg; HR, 448 ± 3bpm, and from sham-ADN-transected PVH-lesioned ( AP, 119 ± 2mm Hg; HR, 391 ± 6bpm and sham-ADN-transected sham-PVH-lesioned animals ( AP, 116 ± 2mHg; HR, 436 ± 4bpm). In the second series of experiments after control AP and HR recordings rats were first subjected to either bilateral lesions of the PVH or sham-PVH lesions, and second to either bilateral ADN transection or sham-ADN transection. PVH lesions did not significantly alter the AP and HR from control levels. However, AP and HR in the ADN-transected rats were significantly higher in the sham-PVH-lesioned rats compared to the PVH-lesioned ADN-transected, PVH-lesioned sham-ADN-transected and sham-PVH-lesioned sham-ADN-transected animals. These data demonstrate that the PVH plays an important role in both the maintenance and development of the increased AP and HR resulting from aortic baroreceptor deafferentation and that these cardiovascular changes are dependent on the integrity of this structure.

Hemodynamic and neural mechanisms of acute neurogenic hypertension in the rat.

Experiments were performed to test the hypothesis that acute hypertension caused by aortic baroreceptor deafferentation (ABD) is the result of sympathetic vasoconstriction. Cardiac output (CO), mean arterial pressure (MAP), and total peripheral resistance (TPR) were measured before and after ABD in anesthetized and conscious rats. The role of the sympathetic nervous system in acute ABD-induced hypertension was evaluated by examining the ability of adrenalectomy, adrenal demedullation, guanethidine or combined adrenal demedullation, and guanethidine pretreatment to prevent, and total autonomic blockade to reverse, ABD-induced hypertension. CO did not change significantly after ABD at any time, whereas MAP and TPR increased significantly (P less than 0.05). Only combined adrenal demedullation and guanethidine pretreatment prevented ABD-induced hypertension, and autonomic blockade normalized MAP in ABD rats. Normalization of blood pressure was the result of a decreased TPR. It is concluded that acute ABD-induced hypertension results from vasoconstriction caused by neurally released and/or circulating catecholamines.

Baroreflex sensitivity and susceptibility to systolic hypertension induced by DOCA-salt in the Sabra rat.

Rats of the salt-resistant Sabra strain (SBN) have a more sensitive baroreflex control of heart rate than do normotensive hypertension-prone salt-sensitive (SBH) rats. To test the hypothesis that increased baroreflex sensitivity confers resistance to hypertension, aortic baroreceptor deafferentation (ABD) was performed in 7- to 10-wk-old SBN rats. This treatment reduced the slope of the mean arterial pressure-heart period (MAP-HP) relationship in response to infusions of increasing doses of phenylephrine in conscious rats, from 1.92 +/- 0.21 to 0.66 +/- 0.11 ms X mmHg-1 (P less than 0.01). The latter value did not differ significantly from that of untreated SBH rats (0.56 +/- 0.07 ms X mmHg-1). Treatment of uniphrectomized SBH, SBN-ABD, and sham-operated SBN rats for 3 wk with deoxycorticosterone acetate (DOCA; 25-mg pellet) and 0.9% NaCl + 0.4% KCl (to maintain normal serum K+ values) as drinking fluid caused increases in systolic blood pressure from 126 +/- 3 to 147 +/- 5 mmHg and 104 +/- 6 to 130 +/- 8 mmHg in the former two groups, respectively, but no significant change (105 +/- 3 to 110 +/- 4 mmHg) in SBN rats when measured by an indwelling arterial catheter in the tail artery. The slopes of the MAP-HP relationships of each of the above three groups of rats were not significantly altered by DOCA-salt treatment. It is concluded that a decrease in baroreflex control of the heart by ABD can render SBN rats sensitive to DOCA-salt-induced systolic hypertension.

Cardiovascular and body fluid changes after aortic baroreceptor deafferentation.

These experiments were performed to determine the role of fluid volume contraction in the compensatory cardiovascular response to an abrupt neurogenically mediated increase in systemic arterial blood pressure. Acute neurogenic hypertension was produced by selective aortic baroreceptor deafferentation (ABD) in the rat. Salt and water balance, fluid compartment volumes, and arterial pressure were measured before and for 5 days after the induction of hypertension by ABD. In rats with ABD, arterial pressure was increased approximately 30 mmHg 1 day after deafferentation and declined 15-20 mmHg over the next 4 days. Plasma volume and extracellular fluid volume were decreased 5 days after ABD. Urine output did not increase after ABD, and the fluid volume contraction was instead the result of a significant decrease in water intake. Sham-operated rats did not exhibit significant changes in any of these parameters. Sodium balance decreased slightly in both sham-operated and ABD rats postsurgery. These results confirm that fluid volume contraction is a prominent compensatory response to an abrupt rise in arterial pressure, but suggest that this compensation is not necessarily mediated through alterations in renal salt and water excretion.

Pathogenesis of hypertension in rats with chronic aortic baroreceptor deafferentation.

In an attempt to produce a form of chronic neurogenic hypertension without the increased blood pressure lability which is characteristic of total baroreceptor removal, selective aortic baroreceptor deafferentation (ABD) was performed in rats. Blood pressure, blood pressure variability, heart rate, plasma and extracellular fluid volumes, and the effect of total autonomic blockade were determined in male rats 1 month following ABD. Rats with ABD had significantly higher systolic, diastolic, and mean arterial blood pressures than did sham-operated animals, but the standard deviation of pressure measured repetitively over a 1-hour period was not significantly greater. Total autonomic blockade with atropine, propranolol, and phentolamine lowered blood pressure and heart rate to a similar level in ABD and sham-operated rats. Extracellular fluid volume was not different in the two groups of rats, but plasma volume was significantly lower in rats with ABD. Despite the overall reduction in plasma volume, there was a significant positive correlation between plasma volume and blood pressure in ABD rats; no such correlation was observed in sham-operated rats. It was concluded that ABD produces a mild, chronic hypertension in rats without marked pressure lability. Although the hypertension appears to be Neurogenic in that it is ABOLIshed by autonomic blockade, volume factors also may contribute to the increased blood pressure.

Actions of sodium and potassium ions on baroreceptors of normotensive and spontaneously hypertensive rats.

Actions of sodium and potassium ions on baroreceptors of normotensive and spontaneously hypertensive rats.